title: Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification.
abstract: We investigated whether octogenarian patients with acute myeloid leukemia enrolled onto Cooperative Group clinical trials and treated with intensive induction therapy could be cured, and whether karyotype and selected molecular markers had any prognostic significance in these patients. Among 138 patients with cytogenetic information, normal karyotype was the most common (47.1%) followed by complex karyotype (14.5%) and sole +8 (9.4%). Among these patients, the relapse-free survival rate at 1 year was 37% and 13% at 3 years, and the respective overall survival rates were 24% and 8%. Whereas the 90 patients who survived beyond 30 days had the same relapse-free survival rates, their 1-year and 3-year overall survival rates were 36% and 11%, respectively. Of the 66 patients surviving beyond 30 days who could be classified into European LeukemiaNet genetic groups, those in the intermediate-I group had better overall survival than patients in the adverse group (P=0.01). Among patients with cytogenetically normal acute myeloid leukemia who were tested for the European LeukemiaNet-associated molecular alterations, FLT3-internal tandem duplication and NPM1 mutations, it was found that FLT3-internal tandem duplication (detected in 29% of patients) did not associate with overall survival (P=0.31), whereas NPM1 mutations (30%) were associated with a significantly longer overall survival (P=0.002). We conclude that intensive induction is effective and indicated in selected octogenarians with acute myeloid leukemia, that their overall survival varies among the European LeukemiaNet genetic groups and that NPM1 mutations may be of prognostic significance among octogenarian patients with cytogenetically normal acute myeloid leukemia.
authors.affiliation: meir.wetzler@roswellpark.org.
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Jessica
authors.initials: J
authors.lastname: Kohlschmidt
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pilorge
authors.forename: Utz
authors.initials: U
authors.lastname: Krug
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchner
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D059786:Abnormal Karyotype; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3